Human skin is susceptible to oxidative stress due to various causes, such as external environmental stressors including exposure to ultraviolet radiation, air pollution, cigarette smoke, chemicals, cosmetics, drugs, ozone and even oxygen itself, as well as to internal stress due to natural biological processes.
For example, the damaging effect of the ultraviolet (UV) part of solar radiation on the skin is well recognized. UV radiation is known to be the predominant cause of premature aging of the skin. UV radiation may lead to photochemical reactions, wherein then the photochemical reaction products intervene in the skin mechanism. Predominantly such photochemical reaction products are free-radical compounds, for example hydroxy radicals. Also, undefined free-radial photoproducts, which are produced in the skin itself, may trigger uncontrolled side reactions due to their high reactivity. Furthermore, lipid peroxidation products, such as for example hydroperoxides and aldehydes, are produced. Free-radical chain reactions may be triggered, resulting in skin damage.
Moreover, UV radiation is ionizing radiation. Hence, there is the risk that ionic species are produced on UV exposure, which species in turn are able to intervene oxidatively in the biochemical processes.
In additional to externally generated oxidative stress, internally generated oxidative stress may occur as a natural by-product of cellular energy production. Both internal and external oxidative stress leads to inflammatory pathways mediated by the formation of free radicals (molecules with unpaired electrons that are highly reactive) that, left unchecked, can cause severe cellular damage to cell membranes, lipids, proteins and DNA. The superoxide radical, a natural by-product of metabolic energy production, causes serious deleterious effects to living cells if not quenched, neutralized or reduced almost immediately after production. It is known that lipid peroxidation is a major problem in biological systems. Protecting against cell membrane oxidation is of paramount importance in living biological systems since the cell membrane is the cell's first line of defense against oxidation
The lifetime summation of damage caused by run-away free radicals is one of the main theories of aging, “the damage accumulation theory of aging”. There is therefore a high interest in modern medicine regarding the use of antioxidants, substances that scavenge and eliminate free radicals, to counter the deleterious effects (i.e., aging) of the free radical mediated inflammatory pathways caused by oxidative stress.
Oxidative damage to the skin and its more detailed causes are discussed in J. Fuchs et al., “Skin Diseases Associated with Oxidative Injury” in “Oxidative Stress in Dermatology”, 1983, pp. 323 et seq.
Antioxidants are substances, to include free radical absorbers or scavengers, that prevent oxidation processes, including oxidation of a molecule such as a lipid, lipoprotein, protein or DNA, or autooxidation of fats containing unsaturated compounds. Various antioxidants are used in the field of cosmetics and pharmacy. These include, for example tocopherol, kinetin, ubiquinone, ascorbic acid, lipoic acid sesamol, colic acid derivatives, butylhydroxy anisole and butylhydroxy toluene. Antioxidants can thus help protect human cells, such as skin cells, from both externally and internally generated oxidative stress.
Topical application of antioxidants is used to optimize the cutaneous antioxidative capacity and to limit skin damage. In vitro and in vivo studies have demonstrates antioxidative and photoprotective properties of antioxidants. See K. Scharffetter-Kochanek et al., “Photoaging of the skin from phenotype to mechanisms”, Exp Gerontol 2000, 35:307-316; and J. Wenk et al., “UV-induced oxidative stress and photoaging”, Curr Probl Dermatol 2001, 29:83-94. Accordingly, antioxidants may be incorporated in the cosmetic or dermatological formulations.
U.S. Pat. No. 6,756,045 describes treating skin changes, for example involving oxidative processes, using idebenone.